Paraoxonase 1 Activity Is Modulated by the rs662 Polymorphism and IgG Anti-High-Density Lipoprotein Antibodies in Patients With Rheumatoid Arthritis: Potential Implications for Cardiovascular Disease

Arthritis & Rheumatology
Javier Rodríguez-CarrioAna Suárez

Abstract

Paraoxonase 1 (PON-1) is a high-density lipoprotein (HDL)-associated antioxidant enzyme that plays an important role in HDL-mediated cardioprotection. Although genetic polymorphisms are known to modulate PON-1 activity, its involvement in cardiovascular disease (CVD) in rheumatoid arthritis (RA) is controversial, suggesting that other factors may modulate its function. Since anti-HDL antibodies have been found to be related to an impaired lipid profile and occurrence of CVD in RA, this study was undertaken to examine the associations between PON-1 activity, anti-HDL antibodies, and CVD according to PON1 genetic variants in patients with RA. Serum PON-1 activity, using paraoxon as substrate, and IgG anti-HDL antibodies were quantified in 212 RA patients and 110 healthy controls. The PON1 rs662 genotype (Q>R) was determined with TaqMan probes. An additional group of 13 biologics-naive patients with RA was prospectively followed up for 3 months. PON-1 activity was decreased in RA patients compared to healthy controls (P = 0.005), and an effect of the rs662 genotype was noted in both groups, with Q/Q homozygotes exhibiting the lowest PON-1 activity. The distribution of rs662 genotypes did not differ between RA patients and healthy ...Continue Reading

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